Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks
Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks
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DOI：
10.1172/jci42680
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发表时间：
2010-08-01
影响因子：
15.9
通讯作者：
Karasuyama, Hajime
中科院分区：
文献类型：
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作者：
Wada, Takeshi;Ishiwata, Kenji;Karasuyama, Hajime
蜱虫是一种体外寄生节肢动物，可以在人类和动物取血过程中传播多种微生物，导致严重的传染性疾病，包括莱姆病。杀螨剂是杀死蜱虫的药物制剂。抗螨蜱的出现要求对蜱和蜱传疾病采取替代控制策略。许多动物在反复感染蜱虫后产生对蜱虫的抵抗力，但这种获得性抗蜱虫免疫的性质仍然知之甚少。在这里，我们研究了小鼠对长角血蜱获得性耐药性的细胞和分子机制，发现抗体是必需的，嗜碱性细胞上的IgFc受体表达也是必需的，而肥大细胞上则不需要。嗜碱性粒细胞的浸润发生在蜱虫第二次侵染时，而不是第一次侵染时。为了评估嗜碱性粒细胞浸润对获得性蜱虫抗性的要求，在肥大细胞蛋白酶8 （Mcpt8）启动子的控制下，产生表达人白喉毒素受体的小鼠。白喉毒素对这些小鼠有选择性地消融嗜碱性细胞。第二次蜱侵害前白喉毒素介导的嗜碱性粒细胞耗竭导致获得性蜱抗性丧失。据我们所知，这些数据提供了第一个明确的证据，证明嗜碱性细胞在抗体介导的对蜱虫的获得性免疫中起着重要而非多余的作用，这可能为控制蜱虫传播疾病提供新的策略。
Ticks are ectoparasitic arthropods that can transmit a variety of microorganisms to humans and animals during blood feeding, causing serious infectious disorders, including Lyme disease. Acaricides are pharmacologic agents that kill ticks. The emergence of acaricide-resistant ticks calls for alternative control strategies for ticks and tick-borne diseases. Many animals develop resistance to ticks after repeated infestations, but the nature of this acquired anti-tick immunity remains poorly understood. Here we investigated the cellular and molecular mechanisms underlying acquired resistance to Haemaphysalis longicornis ticks in mice and found that antibodies were required, as was IgFc receptor expression on basophils but not on mast cells. The infiltration of basophils at tick-feeding sites occurred during the second, but not the first, tick infestation. To assess the requirement for basophil infiltration to acquired tick resistance, mice expressing the human diphtheria toxin receptor under the control of the mast cell protease 8 (Mcpt8) promoter were generated. Diphtheria toxin administration to these mice selectively ablated basophils. Diphtheria toxin-mediated basophil depletion before the second tick infestation resulted in loss of acquired tick resistance. These data provide the first clear evidence, to our knowledge, that basophils play an essential and nonredundant role in antibody-mediated acquired immunity against ticks, which may suggest new strategies for controlling tick-borne diseases.